Enhancing the cellular uptake of cell penetrating peptides by decreasing the membrane dipole potential

Research carried out in collaboration between the Department of Biophysics


Research carried out in collaboration between the Department of Biophysics and Cell Biology, and the Department of Genetics of Applied Microbiology at the University of Debrecen, and the Department of Organic Chemistry, Semmelweis University revealed that cellular uptake of cell penetrating peptides (CPP) depends on the membrane dipole potential and that it can be enhanced by reducing the dipole potential. Cell penetrating peptides are molecules capable of traversing the intact cell membrane even when loaded with cargo, e.g. membrane impermeable drugs. The research group of Peter Nagy found that this uptake takes place by endocytosis followed by endosomal escape. Since most cell penetrating peptides are positively charged, the intramembrane, positive dipole potential generated by the ordered arrangement of dipoles in the membrane, inhibits their membrane crossing. Atorvastatin, widely applied in the treatment of high blood cholesterol levels, decreases the membrane dipole potential and consequently enhances the cellular uptake of cell penetrating peptides. The findings, published in the British Journal of Pharmacology (https://doi.org/10.1111/bph.15509), lay the foundation for applying the revealed principle for boosting the cellular uptake of drugs in the treatment of human diseases.
 

Last update: 2023. 06. 23. 13:37